The Asthma-COPD Overlap Syndrome: A Common Clinical Problem in the Elderly

Abstract

Many patients with breathlessness and chronic obstructive lung disease are diagnosed with either asthma, COPD, or-frequently-mixed disease. More commonly, patients with uncharacterized breathlessness are treated with therapies that target asthma and COPD rather than one of these diseases. This common practice represents the difficulty in distinguishing these disorders clinically, particularly in patients with a history that does not easily differentiate asthma from COPD. A common clinical scenario is an older former smoker with partially reversible or fixed airflow obstruction and evidence of atopy, demonstrating "overlap" features of asthma and COPD. We stress that asthma-COPD overlap syndrome becomes more prevalent with advancing age as patients respond less favorably to guideline-recommended drug therapy. We review the similarities and differences in clinical characteristics between these disorders, and their physiologic and inflammatory profiles within the context of the aging patient. We underscore the difficulties in differentiating asthma from COPD in current or former smokers, share our institutional experience with overlap syndrome, and highlight the need for new research to better characterize and investigate this important clinical phenotype.

Figure 1

The prevalence of obstructive airway diseases in a small cohort of general pulmonary clinic patients at the UC Davis Medical Center. The category of “Other” represents a combination of bronchitis, bronchiectasis, bronchiolitis, and/or cystic fibrosis cases. The numbers within each bar above represent the percentage for that group (*P = 0.0003 and **P = 0.014 by Fisher's exact test). For definitions of the different diagnostic groups, please see the text.

Figure 2

The prevalence of obstructive airway diseases in a small cohort of patients from our the UC Davis Asthma Network (UCAN) severe asthma clinic at the UC Davis Medical Center. The category of “Other” represents a combination of bronchitis, bronchiectasis, and/or bronchiolitis. The numbers within each bar above represent the percentage for that group (*P = 0.0009, **P < 0.0001, and ***P < 0.0001 by Fisher's exact test). For definitions of the different diagnostic groups, please see the text.

Figure 3

The prevalence of obstructive airway diseases in our combined cohort of general pulmonary and UCAN severe asthma clinic patients (N = 146) at the UC Davis Medical Center. The category of “Other” represents a combination of bronchitis, bronchiectasis, bronchiolitis, and/or cystic fibrosis cases. The numbers within each bar above represent the percentage for that group (*P < 0.0001 and **P = 0.0005 by Fisher's exact test). For definitions of the different diagnostic groups, please see the text.

Figure 4

The relative ages of the combined cohort of general pulmonary and UCAN severe asthma clinics at the UC Davis Medical Center. The numbers in each bar represent the mean age per group (*P < 0.0001 by the Kruskal-Wallis test). For definitions of the different diagnostic groups, please see the text.

Figure 5

The age distribution of the N = 29 subjects diagnosed with overlap syndrome in the combined general pulmonary and UCAN severe asthma clinics at the UC Davis Medical Center. The values above each bar represent the percentage of patients within the defined age group (*P = 0.0024 by Fisher's exact test).

Figure 6

Common risk factors for the development of obstructive airways disease. Although asthma, COPD, and asthma-COPD overlap syndrome^† likely share many of the same risk factors, it is unknown whether the overlap syndrome is a unique genotype and pathophysiologically unique clinical phenotype. The progression from early life insults to pediatric disease and finally chronic obstructive airway disease in adulthood involves complex genetic, epigenetic, and environmental interactions. Because the underlying pathogenic mechanisms that lead to the overlap syndrome have not be elucidated, we have no known disease-specific therapies other than those extrapolated from clinical trials done in asthma- or COPD-only subjects. In this lies an opportunity for further research focused on the overlap syndrome as the “third arm” of the most common obstructive airway diseases. Given that asthma-COPD overlap syndrome prevalence increases with age, knowledge about this syndrome will have great clinical and economic implications for our aging population. ^†For definitions of the different diagnostic groups, please see the text. Abbreviations: inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), long-acting muscarinic antagonist (LAMA), leukotriene receptor antagonist (LTRA), 5-lipoxygenase (5-LO), body mass index (BMI), airway hyperreactivity (AHR), and lung volume reduction surgery (LVRS).